A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells (original) (raw)

• Sakaguchi, S., Yamaguchi, T., Nomura, T. & Ono, M. Regulatory T cells and immune tolerance. Cell 133, 775–787 (2008).
  Article CAS PubMed Google Scholar
• Feuerer, M. et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15, 930–939 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Josefowicz, S.Z., Lu, L.F., Rudensky, A.Y. & Regulatory, T. Cells: Mechanisms of differentiation and function. Annu. Rev. Immunol. 30, 531–564 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Curotto de Lafaille, M.A. & Lafaille, J.J. Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30, 626–635 (2009).
  Article CAS PubMed Google Scholar
• Duarte, J.H. et al. Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur. J. Immunol. 39, 948–955 (2009).
  Article CAS PubMed Google Scholar
• Tsuji, M. et al. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323, 1488–1492 (2009).
  Article CAS PubMed Google Scholar
• Murai, M. et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat. Immunol. 10, 1178–1184 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Zhou, X. et al. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 10, 1000–1007 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Rubtsov, Y.P. et al. Stability of the regulatory T cell lineage in vivo. Science 329, 1667–1671 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Komatsu, N. et al. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc. Natl. Acad. Sci. USA 106, 1903–1908 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Hill, J.A. et al. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 27, 786–800 (2007).
  Article CAS PubMed Google Scholar
• Feuerer, M., Hill, J.A., Mathis, D. & Benoist, C. Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat. Immunol. 10, 689–695 (2009).
  Article CAS PubMed Google Scholar
• Vignali, D.A., Collison, L.W. & Workman, C.J. How regulatory T cells work. Nat. Rev. Immunol. 8, 523–532 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Ziegler, S.F. FOXP3: of mice and men. Annu. Rev. Immunol. 24, 209–226 (2006).
  Article CAS PubMed Google Scholar
• Hori, S., Nomura, T. & Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 (2003).
  Article CAS PubMed Google Scholar
• Fontenot, J.D. et al. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22, 329–341 (2005).
  CAS PubMed Google Scholar
• Gavin, M.A. et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445, 771–775 (2007).
  Article CAS PubMed Google Scholar
• Lin, W. et al. Regulatory T cell development in the absence of functional Foxp3. Nat. Immunol. 8, 359–368 (2007).
  Article CAS PubMed Google Scholar
• Otsubo, K. et al. Identification of FOXP3-negative regulatory T-like (CD4+CD25+CD127low) cells in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Clin. Immunol. 141, 111–120 (2011).
  Article CAS PubMed Google Scholar
• Sugimoto, N. et al. Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int. Immunol. 18, 1197–1209 (2006).
  Article CAS PubMed Google Scholar
• Ono, M. et al. Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature 446, 685–689 (2007).
  Article CAS PubMed Google Scholar
• Wu, Y. et al. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 126, 375–387 (2006).
  Article CAS PubMed Google Scholar
• Pan, F. et al. Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells. Science 325, 1142–1146 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Zheng, Y. et al. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses. Nature 458, 351–356 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Zhou, L. et al. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453, 236–240 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Beyer, M. et al. Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation. Nat. Immunol. 12, 898–907 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Chaudhry, A. et al. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326, 986–991 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Shi, L.Z. et al. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 208, 1367–1376 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Dang, E.V. et al. Control of TH17/Treg balance by hypoxia-inducible factor 1. Cell 146, 772–784 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Koch, M.A. et al. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat. Immunol. 10, 595–602 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, Y., Souabni, A., Flavell, R.A. & Wan, Y.Y. An intrinsic mechanism predisposes Foxp3-expressing regulatory T cells to Th2 conversion in vivo. J. Immunol. 185, 5983–5992 (2010).
  Article CAS PubMed Google Scholar
• Gardner, T.S. & Faith, J.J. Reverse-engineering transcription control networks. Phys. Life Rev. 2, 65–88 (2010).
  Article Google Scholar
• Basso, K. et al. Reverse engineering of regulatory networks in human B cells. Nat. Genet. 37, 382–390 (2005).
  Article CAS PubMed Google Scholar
• Battle, A., Segal, E. & Koller, D. Probabilistic discovery of overlapping cellular processes and their regulation. J. Comput. Biol. 12, 909–927 (2005).
  Article CAS PubMed Google Scholar
• Faith, J.J. et al. Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLoS Biol. 5, e8 (2007).
  Article PubMed PubMed Central Google Scholar
• Thornton, A.M. et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433–3441 (2010).
  Article CAS PubMed Google Scholar
• Yu, C. et al. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J. Exp. Med. 195, 1387–1395 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, A.H., Scapa, E.F., Cohen, D.E. & Glimcher, L.H. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320, 1492–1496 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Cai, Q. et al. Helios deficiency has minimal impact on T cell development and function. J. Immunol. 183, 2303–2311 (2009).
  Article CAS PubMed Google Scholar
• Giraud, M. et al. Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells. Proc. Natl. Acad. Sci. USA 109, 535–540 (2012).
  Article CAS PubMed Google Scholar
• Johnson, A.D. et al. λ Repressor and cro—components of an efficient molecular switch. Nature 294, 217–223 (1981).
  Article CAS PubMed Google Scholar
• Pittenger, C. & Kandel, E. A genetic switch for long-term memory. C.R. Acad. Sci. III 321, 91–96 (1998).
  Article CAS PubMed Google Scholar
• Iliopoulos, D., Hirsch, H.A. & Struhl, K. An epigenetic switch involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139, 693–706 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Young, R.A. Control of the embryonic stem cell state. Cell 144, 940–954 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Huehn, J., Polansky, J.K. & Hamann, A. Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat. Rev. Immunol. 9, 83–89 (2009).
  Article CAS PubMed Google Scholar
• Lio, C.W. & Hsieh, C.S. A two-step process for thymic regulatory T cell development. Immunity 28, 100–111 (2008).
  CAS PubMed PubMed Central Google Scholar
• Burchill, M.A. et al. Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity 28, 112–121 (2008).
  CAS PubMed PubMed Central Google Scholar
• Hill, J.A. et al. Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells. Immunity 29, 758–770 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Reich, M. et al. GenePattern 2.0. Nat. Genet. 38, 500–501 (2006).
  Article CAS PubMed Google Scholar
• Rahl, P.B. et al. c-Myc regulates transcriptional pause release. Cell 141, 432–445 (2010).
  Article CAS PubMed PubMed Central Google Scholar